Enterococcus

Enterococcus is a genus of oval-shaped gram-positive cocci that are arranged in pairs or short chains. Distinguishing factors include optochin resistance and the presence of pyrrolidonyl arylamidase (PYR) and Lancefield D antigen. Enterococcus is part of the normal flora of the human GI tract and is frequently involved in nosocomial infections in critically ill or immunocompromised patients, especially those treated with prolonged courses of antibiotics. Common enterococcal infections include urinary tract infections Urinary tract infections Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary Tract Infections, endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis, and intra-abdominal infections. Enterococci are notorious for their intrinsic and acquired resistance to multiple antimicrobials, which makes treatment of enterococcal infections particularly challenging.

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Classification

Microbiology flowchart gram-positive bacteria classification

Gram-positive bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview:
Most bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview can be classified according to a lab procedure called Gram staining.
Bacteria with cell walls that have a thick layer of peptidoglycan retain the crystal violet stain utilized in Gram staining but are not affected by the safranin counterstain. These bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview appear as purple-blue on the stain, indicating that they are gram positive. The bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview can be further classified according to morphology (branching filaments, bacilli, and cocci in clusters or chains) and their ability to grow in the presence of oxygen (aerobic versus anaerobic). The cocci can also be further identified. Staphylococci can be narrowed down on the basis of the presence of the enzyme coagulase and on their sensitivity to the antibiotic novobiocin. Streptococci are grown on blood agar and classified on the basis of which form of hemolysis they employ (α, β, or γ). Streptococci are further narrowed on the basis of their response to the pyrrolidonyl-β-naphthylamide (PYR) test, their sensitivity to specific antimicrobials (optochin and bacitracin), and their ability to grow on sodium chloride (NaCl) media.

Image by Lecturio. License: CC BY-NC-SA 4.0

General Characteristics

Enterococci (formerly classified as group D streptococci) are part of the normal flora of the human GI tract. Fewer than ⅓ of the known species are responsible for clinically significant human disease. 

Genus characteristics

  • Oval-shaped gram-positive cocci 
  • Arranged in pairs or short chains
  • Facultative anaerobes
  • Catalase-negative
  • Optochin-resistant
  • Pyrrolidonyl arylamidase (PYR)–positive
  • Possess Lancefield group D antigen (hence, previously classified as group D streptococci)
  • Can be cultured in bile media and 6.5% NaCl
  • Clinically significant human pathogens (most common):
    • Enterococcus faecalis 
    • E. faecium
Enterococcus faecalis

Enterococcus faecalis

Image: “Enterococcus faecalis20023-300” by Gzuckier. License: Public Domain

Pathogenesis

Enterococci most commonly appear in nosocomial infections.

  • Reservoir: human GI tract
  • Transmission:
    • Translocation from colonization site in the colonized patient (frequently associated with GI and genitourinary procedures)
    • Transmission to health care workers and other patients through direct contact, fecal–oral transmission, or fomites
  • Virulence factors:
    • Antimicrobial resistance:
      • Intrinsic (beta-lactam antibiotics (through penicillin-binding proteins), trimethoprim Trimethoprim The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. Sulfonamides and Trimethoprim–sulfamethoxazole, low levels of clindamycin and aminoglycosides Aminoglycosides Aminoglycosides are a class of antibiotics including gentamicin, tobramycin, amikacin, neomycin, plazomicin, and streptomycin. The class binds the 30S ribosomal subunit to inhibit bacterial protein synthesis. Unlike other medications with a similar mechanism of action, aminoglycosides are bactericidal. Aminoglycosides)
      • Acquired (beta-lactam antibiotics (through beta-lactamases), high-level aminoglycosides Aminoglycosides Aminoglycosides are a class of antibiotics including gentamicin, tobramycin, amikacin, neomycin, plazomicin, and streptomycin. The class binds the 30S ribosomal subunit to inhibit bacterial protein synthesis. Unlike other medications with a similar mechanism of action, aminoglycosides are bactericidal. Aminoglycosides, tetracycline, fluoroquinolones Fluoroquinolones Fluoroquinolones are a group of broad-spectrum, bactericidal antibiotics inhibiting bacterial DNA replication. Fluoroquinolones cover gram-negative, anaerobic, and atypical organisms, as well as some gram-positive and multidrug-resistant (MDR) organisms. Fluoroquinolones, rifampin, chloramphenicol Chloramphenicol Chloramphenicol, the only clinically relevant drug in the amphenicol class, is a potent inhibitor of bacterial protein synthesis by binding to the 50S ribosomal subunit and preventing peptide bond formation. Chloramphenicol is a broad-spectrum antibiotic with wide distribution; however, due to its toxicity, its use is limited to severe infections. Chloramphenicol, and vancomycin)
    • Biofilm formation:
      • Protects against host defenses
      • Allows gene exchange (further promoting antibiotic resistance) 
  • Host factors that increase susceptibility:
    • Critical illness
    • Receiving lengthy courses of antibiotics
    • Hematologic malignancies
    • Solid organ transplantation Organ Transplantation Transplantation is a procedure that involves the removal of an organ or living tissue and placing it into a different part of the body or into a different person. Organ transplantations have become the therapeutic option of choice for many individuals with end-stage organ failure. Organ Transplantation

Clinical Relevance

Epidemiology

  • Enterococci are 1 of the top 3 species causing nosocomial infections.
  • 4th most common cause of nosocomial bloodstream infections in the United States
  • 35%–40% of enterococcal bloodstream infections involve vancomycin-resistant E. faecium (VRE)

Diseases caused by enterococci

  • Often associated with:
    • Indwelling catheters
    • Surgical instrumentation
    • Underlying structural abnormalities
  • Common infections associated with Enterococcus include:
    • Urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract infections (most common)
    • Endocarditis
    • Bacteremia
    • Intra-abdominal and pelvic infections (often cholecystitis Cholecystitis Cholecystitis is the inflammation of the gallbladder (GB) usually caused by the obstruction of the cystic duct (acute cholecystitis). Mechanical irritation by gallstones can also produce chronic GB inflammation. Cholecystitis is one of the most common complications of cholelithiasis but inflammation without gallstones can occur in a minority of patients. Cholecystitis)
    • Wound infections
  • Other less common infections:
    • Meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis
    • Pleural space infection
    • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin/soft tissue infections

Organism isolation

  • Blood cultures: susceptibility testing should be included to choose appropriate therapy
  • Stool and perirectal cultures: to evaluate for VRE colonization

Antibiotic selection

  • Monotherapy:
    • May be appropriate in noncritically ill patients without endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis
    • Ampicillin is the drug of choice for susceptible species.
  • Combination therapy: 
    • Most commonly used in practice
    • For endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis and all critically ill patients
    • Cell-wall inhibitor (ampicillin, ceftriaxone, vancomycin) + aminoglycoside 
    • Often ampicillin and gentamicin
  • VRE infections:
    • Linezolid
    • Daptomycin
    • Tigecycline
  • In addition to antibiotic therapy:
    • All indwelling line and catheters should be removed.
    • Abscesses should be drained.

References

  1. Riedel S., et al. (2019). In Jawetz, Melnick & Adelberg’s Medical Microbiology, pp. 215–233.
  2. Murray, B., Miller, W. (2021). Microbiology of enterococci. UpToDate. Retrieved May 01, 2021, from https://www.uptodate.com/contents/microbiology-of-enterococci
  3. Murray, B., Miller, W. (2021). Treatment of enterococcal infections. UpToDate. Retrieved May 01, 2021, from https://www.uptodate.com/contents/treatment-of-enterococcal-infections
  4. Fraser S.L. (2018). Enterococcal infections treatment & management. https://emedicine.medscape.com/article/216993-treatment

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